Medicine and Health Sciences Commons^™

Promoting Adherence And Retention To Clinical Trials In Special Populations: A Women's Health Initiative Workshop, Sara Wilcox, Sally Shumaker, Deborah Bowen, Michelle Naughton, Milagros Rosal, Shari Ludlam, Elizabeth Dugan, Julie Hunt, Stephanie Stevens

Elizabeth Dugan

This paper describes a Women's Health Initiative workshop on promoting adherence and retention in randomized clinical trials among ethnic minority women, participants of lower socioeconomic status, and older women. Workshop objectives were: (1) to increase knowledge of demographic and cultural characteristics of diverse groups, (2) to increase awareness of how diversity can affect interactions in clinical research, (3) to explore how research staff behavior can influence adherence and retention, and (4) to increase knowledge of strategies to enhance adherence and retention in special populations. The workshop emphasized the importance of understanding beliefs, values, and experiences that are common in diverse …

Development Of Abbreviated Measures To Assess Patient Trust In A Physician, A Health Insurer, And The Medical Profession, Elizabeth Dugan, Felicia Trachtenberg, Mark Hall

Elizabeth Dugan

BACKGROUND: Despite the recent proliferation in research on patient trust, it is seldom a primary outcome, and is often a peripheral area of interest. The length of our original scales to measure trust may limit their use because of the practical needs to minimize both respondent burden and research cost. The objective of this study was to develop three abbreviated scales to measure trust in: (1) a physician, (2) a health insurer, and (3) the medical profession. METHODS: Data from two samples were used. The first was a telephone survey of English-speaking adults in the United States (N = 1117) …

Patient Education About Anticoagulant Medication: Is Narrative Evidence Or Statistical Evidence More Effective?, Kathleen Mazor, Joann Baril, Elizabeth Dugan, Frederick Spencer, Pamela Burgwinkle, Jerry Gurwitz

Elizabeth Dugan

OBJECTIVE: To determine the relative impact of incorporating narrative evidence, statistical evidence or both into patient education about warfarin, a widely used oral anticoagulant medication.

METHODS: 600 patients receiving anticoagulant therapy were randomly assigned to view one of three versions of a video depicting a physician-patient encounter where anticoagulation treatment was discussed, or usual care (no video). The videos differed in whether the physician used narrative evidence (patient anecdotes), statistical evidence, or both to highlight key information. 317 patients completed both the baseline and post-test questionnaires. Questions assessed knowledge, beliefs and adherence to medication and laboratory monitoring regimens.

RESULTS: All …

Nitric Oxide-Mediated Inhibition Of Hdm2-P53 Binding, Christopher Schonhoff, Marie-Claire Daou, Stephen Jones, Celia Schiffer, Alonzo Ross

Celia A. Schiffer

It has become increasingly evident that nitric oxide exerts its effects, in part, by S-nitrosylation of cysteine residues. We tested in vitro whether nitric oxide may indirectly control p53 by S-nitrosylation and inactivation of the p53 negative regulator, Hdm2. Treatment of Hdm2 with a nitric oxide donor inhibits Hdm2-p53 binding, a critical step in Hdm2 regulation of p53. The presence of excess amounts of cysteine or dithiothreitol blocks this inhibition of binding. Moreover, nitric oxide inhibition of Hdm2-p53 binding was found to be reversible. Sulfhydryl sensitivity and reversibility are consistent with nitrosylation. Finally, we have identified a critical cysteine residue …

Co-Evolution Of Nelfinavir-Resistant Hiv-1 Protease And The P1-P6 Substrate, Madhavi Kolli, Stephane Lastere, Celia Schiffer

Celia A. Schiffer

The selective pressure of the competitive protease inhibitors causes both HIV-1 protease and occasionally its substrates to evolve drug resistance. We hypothesize that this occurs particularly in substrates that protrude beyond the substrate envelope and contact residues that mutate in response to a particular protease inhibitor. To validate this hypothesis, we analyzed substrate and protease sequences for covariation. Using the chi2 test, we show a positive correlation between the nelfinavir-resistant D30N/N88D protease mutations and mutations at the p1-p6 cleavage site as compared to the other cleavage sites. Both nelfinavir and the substrate p1-p6 protrude beyond the substrate envelope and contact …

Point Mutants Of Ehec Intimin That Diminish Tir Recognition And Actin Pedestal Formation Highlight A Putative Tir Binding Pocket, Hui Liu, Padhma Radhakrishnan, Loranne Magoun, Moses Prabu-Jeyabalan, Kenneth Campellone, Pamela Savage, Feng He, Celia Schiffer, John Leong

Celia A. Schiffer

Attachment to host cells by enterohaemorrhagic Escherichia coli (EHEC) is associated with the formation of a highly organized cytoskeletal structure containing filamentous actin, termed an attaching and effacing (AE) lesion. Intimin, an outer membrane protein of EHEC, is required for the formation of AE lesions, as is Tir, a bacterial protein that is translocated into the host cell to function as a receptor for intimin. We established a yeast two-hybrid assay for intimin-Tir interaction and, after random mutagenesis, isolated 24 point mutants in intimin, which disrupted Tir recognition in this system. Analysis of 11 point mutants revealed a correlation between …

Structural And Thermodynamic Basis For The Binding Of Tmc114, A Next-Generation Human Immunodeficiency Virus Type 1 Protease Inhibitor, Nancy King, Moses Prabu-Jeyabalan, Ellen Nalivaika, Piet Wigerinck, Marie-Pierre De Bethune, Celia Schiffer

Celia A. Schiffer

TMC114, a newly designed human immunodeficiency virus type 1 (HIV-1) protease inhibitor, is extremely potent against both wild-type (wt) and multidrug-resistant (MDR) viruses in vitro as well as in vivo. Although chemically similar to amprenavir (APV), the potency of TMC114 is substantially greater. To examine the basis for this potency, we solved crystal structures of TMC114 complexed with wt HIV-1 protease and TMC114 and APV complexed with an MDR (L63P, V82T, and I84V) protease variant. In addition, we determined the corresponding binding thermodynamics by isothermal titration calorimetry. TMC114 binds approximately 2 orders of magnitude more tightly to the wt enzyme …

Lack Of Synergy For Inhibitors Targeting A Multi-Drug-Resistant Hiv-1 Protease, Nancy King, Laurence Melnick, Moses Prabu-Jeyabalan, Ellen Nalivaika, Shiow-Shong Yang, Yun Gao, Xiaoyi Nie, Charles Zepp, Donald Heefner, Celia Schiffer

Celia A. Schiffer

The three-dimensional structures of indinavir and three newly synthesized indinavir analogs in complex with a multi-drug-resistant variant (L63P, V82T, I84V) of HIV-1 protease were determined to approximately 2.2 A resolution. Two of the three analogs have only a single modification of indinavir, and their binding affinities to the variant HIV-1 protease are enhanced over that of indinavir. However, when both modifications were combined into a single compound, the binding affinity to the protease variant was reduced. On close examination, the structural rearrangements in the protease that occur in the tightest binding inhibitor complex are mutually exclusive with the structural rearrangements …

Contribution Of Ser386 And Ser396 To Activation Of Interferon Regulatory Factor 3, Weijun Chen, Hema Srinath, Suvana Lam, Celia Schiffer, William Royer, Kai Lin

Celia A. Schiffer

IRF-3, a member of the interferon regulatory factor (IRF) family of transcription factors, functions in innate immune defense against viral infection. Upon infection, host cell IRF-3 is activated by phosphorylation at its seven C-terminal Ser/Thr residues: (385)SSLENTVDLHISNSHPLSLTS(405). This phosphoactivation triggers IRF-3 to react with the coactivators, CREB-binding protein (CBP)/p300, to form a complex that activates target genes in the nucleus. However, the role of each phosphorylation site for IRF-3 phosphoactivation remains unresolved. To address this issue, all seven Ser/Thr potential phosphorylation sites were screened by mutational studies, size-exclusion chromatography, and isothermal titration calorimetry. Using purified proteins, we show that CBP …

Time As A Catalyst For Tension In Nurse-Surgeon Communication, Sherry Espin, Lorelei Lingard

Lorelei Lingard

Carefully studying communication patterns between nurses and surgeons questions popular stereotypes about OR discourse and expands educators' understanding of the factors that motivate team communication, patterns that are habitual among team members, and issues that act as catalysts for tension. This study examines the nature of communication between perioperative nurses and surgeons and identifies patterns and sites of tension. Researchers observed 128 hours of interaction between nurses and surgeons in four surgical divisions at one teaching hospital in Ontario, Canada. Field notes were read, coded, and analyzed independently. Results showed that higher tension in nurse-surgeon communication clusters around particular themes, …

Antibiotics For Bronchiolitis In Children, Geoffrey Spurling, Jenny Doust, Chris Del Mar, Lars Ericksson

Jenny Doust

Background: Bronchiolitis is a serious, potentially life-threatening respiratory illness commonly affecting babies. It is often caused by respiratory syncytial virus (RSV). Antibiotics are not recommended for bronchiolitis unless there is concern about complications such as secondary bacterial pneumonia or respiratory failure. Nevertheless, they are used at rates of 34% to 99% in uncomplicated cases. Objectives: To evaluate the effectiveness of antibiotics for bronchiolitis. Search strategy: We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2010, issue 4), which includes the Cochrane Acute Respiratory Infection Group’s Specialised Register, and the Database of Abstracts of Reviews of Effects, MEDLINE (January 1966 …

Alcohol And Hepatitis C Virus--Interactions In Immune Dysfunctions And Liver Damage, Gyongyi Szabo, Jack Wands, Ahment Eken, Natalia Osna, Steven Weinman, Keigo Machida, Joe Wang

Gyongyi Szabo

Hepatitis C virus infection affects 170 million people worldwide, and the majority of individuals exposed to HCV develop chronic hepatitis leading to progressive liver damage, cirrhosis, and hepatocellular cancer. The natural history of HCV infection is influenced by genetic and environmental factors of which chronic alcohol use is an independent risk factor for cirrhosis in HCV-infected individuals. Both the hepatitis C virus and alcohol damage the liver and result in immune alterations contributing to both decreased viral clearance and liver injury. This review will capture the major components of the interactions between alcohol and HCV infection to provide better understanding …

Factors That Determine The Development And Progression Of Gastroesophageal Varices In Patients With Chronic Hepatitis C, Robert Fontana, Arun Sanyal, Marc Ghany, William Lee, Andrea Reid, Deepa Naishadham, Gregory Everson, Jeffrey Kahn, Adrian Di Bisceglie, Gyongyi Szabo, Timothy Morgan, James Everhart

Gyongyi Szabo

BACKGROUND and AIMS: We aimed to identify the incidence and predictors of de novo gastroesophageal variceal formation and progression in a large cohort of patients with chronic hepatitis C and advanced fibrosis. METHODS: All participants in the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis Trial were offered an endoscopy before treatment and again after 4 years. Patients with varices at baseline also had an endoscopy at 2 years. Baseline laboratory and clinical parameters were analyzed as predictors of de novo variceal formation and variceal progression. RESULTS: De novo varices developed in 157 of the 598 (26.2%) patients. Most of the …

The 40th Anniversary Of The National Institute On Alcoholism And Alcohol Abuse: The Impact On Liver Disease, Gyongyi Szabo

Gyongyi Szabo

No abstract provided.

Alcohol Exposure As A Risk Factor For Adverse Outcomes In Elective Surgery, Bharath Nath, Youfu Li, James Carroll, Gyongyi Szabo, Jennifer Tseng, Shimul Shah

Gyongyi Szabo

BACKGROUND AND AIMS: Alcohol consumption is a well-documented determinant of adverse perioperative outcome. We sought to determine the effect of active alcohol consumption following elective surgery. METHODS: We queried discharge records from the American College of Surgeons' National Surgical Quality Improvement Program (NSQIP, 2005-2007) for all elective adult admissions. The 7,631 (2.5%) patients with documented alcohol use (active alcohol use of at least two drinks per day within 2 weeks of surgery; ETOH use) underwent elective surgery; 301,994 (97.5%) patients denied ETOH use. Multivariate analysis was performed with adjustments for demographic and comorbid factors. Primary outcome measures included length of …

Declining Length Of Stay For Patients Hospitalized With Ami: Impact On Mortality And Readmissions, Jane Saczynski, Darleen Lessard, Frederick Spencer, Jerry Gurwitz, Joel Gore, Jorge Yarzebski, Robert Goldberg

Jorge L. Yarzebski

BACKGROUND: Length of hospital stay after acute myocardial infarction decreased significantly in the 1980s and 1990s. Whether length of stay has continued to decrease during the 2000s, and the impact of decreasing length of stay on rehospitalization and mortality, is unclear. We describe decade-long (1995-2005) trends in length of stay after acute myocardial infarction, and examine whether declining length of stay has impacted early rehospitalization and postdischarge mortality in a population-based sample of hospitalized patients.

METHODS: The study sample consisted of 4184 patients hospitalized with acute myocardial infarction in a central New England metropolitan area during 6 annual periods (1995, …

Management And Outcomes Of Renal Disease And Acute Myocardial Infarction, Paul Santolucito, Dennis Tighe, David Mcmanus, Jorge Yarzebski, Darleen Lessard, Joel Gore, Robert Goldberg

Jorge L. Yarzebski

BACKGROUND: Contemporary trends in the management and outcomes of chronic kidney disease patients who develop an acute myocardial infarction have not been adequately described, particularly from the more generalizable perspective of a population-based investigation. METHODS: The study population consisted of 6219 residents of the Worcester, Massachusetts, metropolitan area who were hospitalized with acute myocardial infarction in 6 annual periods between 1995 and 2005. Patients were categorized as having preserved kidney function (n=3154), mild to moderate chronic kidney disease (n=2313), or severe chronic kidney disease (n=752) at the time of hospital admission. RESULTS: Patients with chronic kidney disease were more likely …